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Pharmaceutics
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Targeted Drug Delivery to Improve Cancer Therapy, 2nd Edition
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Targeted Drug Delivery to Improve Cancer Therapy, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (20 July 2025) | Viewed by 3139

Special Issue Editor

Dr. Joseph Anthoney Vetro

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA
Interests: targeted drug delivery; nanoscale dosage forms; nucleic acid therapeutics; small-molecule drugs; antineoplastics; immunological agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Increasing the localization of drugs to hematologic or solid tumor cancer cells by targeted drug delivery holds great promise to improve the treatment of cancer with conventional and nonconventional drugs. Given the broad range of drug types, cancers, and tumor heterogeneities, the successful clinical application of targeted drug delivery will continue to require the preclinical development of multiple drug delivery approaches for selection and further clinical development.

This Special Issue seeks to highlight original research articles and reviews on the preclinical development of targeted drug delivery approaches to improve the pharmacotherapy of cancer with conventional and nonconventional drugs. Research areas include any approaches that improve the treatment of preclinical cancer models with small-molecule (<900 Da) or macromolecule drugs (e.g., biomolecules) (e.g., increase potency and/or efficacy, decrease toxicity) by increasing the localization to the site of action in hematologic cancer cells or solid tumor/tumor-associated cells in primary and/or secondary tumors.

Dr. Joseph Anthoney Vetro
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • local drug delivery
  • systemic drug delivery
  • physical drug delivery
  • passive drug delivery
  • targeted drug delivery
  • nanoscale dosage forms
  • nanomedicine

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Related Special Issue

Published Papers (3 papers)

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Research

24 pages, 4513 KiB  
Article
Anticancer Activity of Paclitaxel-Loaded Mesoporous Silica Nanoparticles in B16F10 Melanoma-Bearing Mice
by Jihoon Lee, Jung Mo Kim, Yeon-Ju Baek, Hyojeung Kang, Min-Koo Choi and Im-Sook Song
Pharmaceutics 2025, 17(8), 1042; https://doi.org/10.3390/pharmaceutics17081042 - 11 Aug 2025
Viewed by 404
Abstract
Background/Objectives: Paclitaxel (PTX) faces clinical limitations in melanoma treatment due to poor solubility, P-glycoprotein (P-gp)-mediated efflux, and systemic toxicity. This study aimed to develop PTX-loaded mesoporous silica nanoparticles (PS), which would be co-administered with curcumin (CUR) and D-α-tocopherol polyethylene glycol 1000 succinate [...] Read more.
Background/Objectives: Paclitaxel (PTX) faces clinical limitations in melanoma treatment due to poor solubility, P-glycoprotein (P-gp)-mediated efflux, and systemic toxicity. This study aimed to develop PTX-loaded mesoporous silica nanoparticles (PS), which would be co-administered with curcumin (CUR) and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) to enhance intracellular accumulation and improve anti-tumor activity. CUR and TPGS were integrated with PS to inhibit P-gp-mediated PTX-efflux, to enhance the intracellular accumulation of PTX, and to improve anti-tumor activity in B16F10 cells. Methods: The physicochemical properties of PS were analyzed using standard characterization methods. The antitumor activity of PS co-administered with CUR and TPGS was evaluated using two-dimensional (2D) culture and three-dimensional (3D) spheroid assays, and also assessed in B16F10 tumor-bearing mice. The therapeutic mechanism of the PS combination was compared using apoptosis and microtubule disruption through flow cytometry and confocal microscopy. The pharmacokinetics and biodistribution of the PS combination were compared in B16F10 tumor-bearing mice. Results: PS formulations exhibited amorphous transformation with an approximate particle size of 200 nm. PS co-administered with CUR and TPGS reduced the IC50 to 178.7 nM compared with 283.3 nM for free PTX in B16F10 melanoma cells and achieved significant tumor growth inhibition in B16F10 melanoma spheroid culture. The intracellular accumulation of PTX correlated with its therapeutic efficacy. Flow cytometry revealed a significant induction of both early and late apoptosis in cells treated with the PS + CUR + TPGS combination, while confocal imaging confirmed enhanced microtubule disruption. In B16F10 tumor-bearing mice, PS co-administered with CUR and TPGS demonstrated higher and selective distribution of PTX into tumor tissue without affecting systemic exposure of PTX in B16F10-xenografted mice. Conclusions: PS + CUR + TPGS combination enhanced PTX delivery by improving solubility and enhancing distribution to tumor tissue through P-gp inhibition, thereby increasing its therapeutic potential. The combination of CUR and TPGS offers synergistic apoptosis induction and microtubule disruption. Thus, the PS + CUR + TPGS combination represents a promising approach for treating drug-resistant melanomas. Full article
(This article belongs to the Special Issue Targeted Drug Delivery to Improve Cancer Therapy, 2nd Edition)
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26 pages, 3841 KiB  
Article
Palladium Complex-Loaded Magnetite Nanoparticles as Drug Delivery Systems for Targeted Liver Cancer Therapy
by Sara A. M. El-Sayed, Ghadha Ibrahim Fouad, Hanan H. Beherei, Mohamed R. Shehata and Mostafa Mabrouk
Pharmaceutics 2025, 17(8), 1033; https://doi.org/10.3390/pharmaceutics17081033 - 8 Aug 2025
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Abstract
Background/Objectives: Liver cancer is considered one of the most dangerous types of cancer due to both the patients’ and the physician’s delay in diagnosis. Metal/ligand complexes represent antitumor drugs; however, they have several limitations such as a lack of specificity that results [...] Read more.
Background/Objectives: Liver cancer is considered one of the most dangerous types of cancer due to both the patients’ and the physician’s delay in diagnosis. Metal/ligand complexes represent antitumor drugs; however, they have several limitations such as a lack of specificity that results in damage to healthy organs. Therefore, there is a need for a material that improves specificity and decreases side effects. Magnetite nanoparticles (MNPs) show outstanding findings in the targeting and treatment of cancer-diseased organs. Methods: Herein, a metal/ligand palladium complex with antitumor activity was prepared and loaded onto magnetite nanoparticles for the treatment of liver cancer. The proposed structures with the lowest energy geometries were identified by density functional theory (DFT) utilizing the Gaussian09 program. Molecular docking simulation was conducted on an HP Pavilion dv6 Notebook PC equipped with an AMD Phenom™ N930 Quad processor. Afterward, the prepared nano-systems were investigated using FTIR and TEM. In vitro drug release measurement was evaluated in PBS at different time intervals. Eventually, the selectivity of these nano-systems was investigated using an animal rat model. Results: The results showed that MNPs with a crystalline structure and superparamagnetic characteristics (Ms = 71.273 emu/g) were created with a large surface area (63.75 m2/g), and they were validated to be acceptable for drug delivery applications. The palladium complex [Pd(DMEN)Cl2] loaded onto magnetite released highly in acidic circumstances (pH 4.5), implying that it could be employed for targeted therapy of liver cancer. Conclusions: In vivo investigations in a rat model of liver cancer induced by diethylnitrosamine and thioacetamide (DEN/TAA) showed that the combination of the palladium complex and magnetite demonstrated a potent anticancer therapeutic activity on liver cancer in rats, improving liver function and structure while mitigating inflammation. Full article
(This article belongs to the Special Issue Targeted Drug Delivery to Improve Cancer Therapy, 2nd Edition)
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27 pages, 3833 KiB  
Article
The Influence of Indisulam on Human Immune Effector Cells: Is a Combination with Immunotherapy Feasible?
by Lisa Arnet, Lisabeth Emilius, Annett Hamann, Maria Carmo-Fonseca, Carola Berking, Jan Dörrie and Niels Schaft
Pharmaceutics 2025, 17(3), 368; https://doi.org/10.3390/pharmaceutics17030368 - 14 Mar 2025
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Abstract
Background: As a modulator of pre-mRNA splicing, the anti-cancer agent indisulam can induce aberrantly spliced neoantigens, enabling immunologic anti-tumor activity. Consequently, combining indisulam with immunotherapy is expected to be a promising novel approach in cancer therapy. However, a prerequisite for such a combination [...] Read more.
Background: As a modulator of pre-mRNA splicing, the anti-cancer agent indisulam can induce aberrantly spliced neoantigens, enabling immunologic anti-tumor activity. Consequently, combining indisulam with immunotherapy is expected to be a promising novel approach in cancer therapy. However, a prerequisite for such a combination is that immune effector cells remain functional and unharmed by the chemical. Methods: To ensure the immunocompetence of human immune effector cells is maintained, we investigated the influence of indisulam on ex vivo-isolated T cells and monocyte-derived dendritic cells (moDCs) from healthy donors. We used indisulam concentrations from 0.625 µM to 160 µM and examined the impact on the following: (i) the activation of CD4+ and CD8+ T cells by CD3-crosslinking and via a high-affinity TCR, (ii) the cytotoxicity of CD8+ T cells, (iii) the maturation process of moDCs, and (iv) antigen-specific CD8+ T cell priming. Results: We observed dose-dependent inhibitory effects of indisulam, and substantial inhibition occurred at concentrations around 10 µM, but the various functions of the immune system exhibited different sensitivities. The weaker activation of T cells via CD3-crosslinking was more sensitive than the stronger activation via the high-affinity TCR. T cells remained capable of killing tumor cells after treatment with indisulam up to 40 µM, but T cell cytotoxicity was impaired at 160 µM indisulam. While moDC maturation was also rather resistant, T cell priming was almost completely abolished at a concentration of 10 µM. Conclusions: These effects should be considered in possible future combinations of immunotherapy with the mRNA splicing inhibitor indisulam. Full article
(This article belongs to the Special Issue Targeted Drug Delivery to Improve Cancer Therapy, 2nd Edition)
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